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By Phil Stewart and Lisa Barrington WASHINGTON/BEIRUT (Reuters) - U.S. Defense Secretary Jim Mattis dismissed concerns on Thursday that the United States was being dragged into a broader conflict in Syria, after a major clash with pro-Syrian government forces overnight that may have left 100 or more of them dead. The U.S.-led coalition said it repelled an unprovoked attack near the Euphrates River by hundreds of troops aligned with Syrian President Bashar al-Assad, who were backed by artillery, tanks, multiple-launch rocket systems and mortars. The incident underscored the potential for further conflict in Syria's oil-rich east, where the U.S.-backed Syrian Democratic Forces (SDF) alliance of Kurdish and Arab militias holds swathes of land after its offensive against Islamic State. Assad, who is supported by Russia and by Shi'ite militias backed by Iran, has said he wants to take back every inch of Syria. The pro-government forces were "likely seeking to seize oilfields in Khusham" east of the Euphrates in Deir al-Zor province, said a U.S. official on condition of anonymity. U.S. Senator Tim Kaine, who sits on Senate foreign relations and military oversight committees, said the episode raised serious concerns about the open-ended U.S. military presence in Syria. "I am gravely concerned that the Trump administration is purposefully stumbling into a broader conflict, without a vote of Congress or clear objectives," Kaine said. Mattis described the attack on the U.S.-backed fighters, who were accompanied by U.S. special operations forces, as "perplexing." But he described the retaliatory U.S.-led coalition strikes as defensive and limited in nature. Asked whether the U.S. military was stumbling into Syria's broader conflict, Mattis said: "No. This is self-defense." "If we were getting involved in a broader conflict, then it would have had an initiative on our part," Mattis told reporters at the Pentagon. No U.S. or U.S.-backed forces died but the U.S. official who spoke anonymously estimated that more than 100 pro-Syrian government forces were killed in the counter-attack. Syrian state television reported that the coalition had caused "dozens of dead and wounded" by bombing pro-government forces. But a commander in the military alliance supporting Assad disputed the death toll, saying seven members of the pro-government forces were killed and 27 injured. In a letter to the United Nations, Syria's foreign ministry described the strike as a "war crime" and called for the coalition to be dismantled, Syrian state news agency SANA said. "We demand (that the international community) condemn this massacre and hold the coalition responsible for it." U.S. TELLS SYRIA: WE'RE NOT SEEKING CONFLICT The U.S.-led coalition was set up in 2014 to battle Islamic State fighters in both Syria and Iraq, who were largely defeated last year. Some 2,000 U.S. forces remain on the ground in Syria, allied to the Kurdish-led SDF alliance, which holds the largest swathe of territory still outside the control of the government. The Syrian civil war, now entering its eighth year, has killed hundreds of thousands of people and driven more than 11 million from their homes, while drawing in regional countries and global powers supporting client factions on the ground. U.S. forces in Syria have already faced direct threats from Syrian and Iranian-backed forces, leading to the shoot-down of Iranian drones and a Syrian jet last year, as well as to tensions with Russia. But this may have been the largest single assault on a U.S.-accompanied position to date. Still, these episodes have been sporadic. U.S.-backed SDF and the pro-Syrian forces had largely avoided direct confrontation while both were fighting the common Islamic State enemy. Moscow and Washington maintain contacts in eastern Syria to prevent unexpected confrontation between forces they support. Pentagon spokeswoman Dana White told a news briefing that Washington was not "looking for a conflict with the regime." Still, the incident underscored growing tensions in Syria amid reports of Syrian chemical weapons use elsewhere in the country. The U.S. State Department on Thursday deplored the alleged use of chemical weapons and backed a call from the United Nations to put violence in Syria on pause for a month in order to deliver humanitarian aid and facilitate the evacuation of civilians. Russia said the proposal was a non-starter. "That's not realistic. We would like to see a ceasefire, the end of war in Syria, but the terrorists, I’m not sure they are in agreement," said Russian U.N. Ambassador Vassily Nebenzia of the proposed one-month ceasefire. SKIRMISHES The coalition said the attack occurred around 8 km (5 miles) "east of the Euphrates River de-confliction line in Khusham", a town southeast of the provincial capital, Deir al-Zor. The U.S.-led coalition had alerted Russian officials about the presence of SDF forces, the U.S. official said. One SDF fighter was wounded, the official said. Nouri Mahmoud, spokesman for the SDF's most powerful element, the Kurdish YPG militia, described the clash as "skirmishes" and said each side had returned to their former positions. "We suspect Syrian pro-regime forces were attempting to seize terrain SDF had liberated from Daesh (Islamic State) in September 2017," the U.S. official said. Russia's Interfax cited the Defence Ministry as saying the incident showed the U.S. goal in Syria was not to battle Islamic State but "the capture and withholding of the economic assets", an apparent reference to the Khusham oil field. Russia's Defence Ministry said the pro-government militias involved in the incident had been carrying out reconnaissance and their activities had not been previously agreed with Russia. (Reporting by Phil Stewart, Idrees Ali and Lisa Lambert in Washington, Lisa Barrington and Dahlia Nehme in Beirut, Vladimir Soldatkin in Moscow and Michelle Nichols at the United Nations; Editing by Peter Graff, James Dalgleish and Lisa Shumaker)